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CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis

Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20717-22. doi: 10.1073/pnas.1321139110. Epub 2013 Dec 2.

Abstract

Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+) myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs.

Keywords: mouse models; protease; stromal cells; vascular pericytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Animals
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • CD11b Antigen
  • CD13 Antigens*
  • Cell Line, Tumor
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Myeloid Cells / metabolism*
  • Myeloid Cells / pathology
  • Neoplasm Metastasis
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology

Substances

  • Angiogenesis Inducing Agents
  • CD11b Antigen
  • CD13 Antigens